Coordinate changes in brain energy metabolism and protein synthesis have been investigated using several models of altered brain metabolism in order to elucidate physiologically relevant mechanisms for the control of protein synthesis. Experimental systems have included transient ischemia in gerbils, amphetamine-induced hyperthermia in mice and electroconvulsive shock in rabbits. During transient ischemia in gerbils brain metabolism is drastically altered. Within 30 minutes of reperfusion, most measures of energy metabolism have returned to control levels, while brain protein synthesis recovers over several hours. Of the several metabolites measured, we have found that only glycogen shows a delayed recovery comparable to that observed for protein synthesis, suggesting the involvement of a common regulatory mechanism. Current efforts focus on determining the phosphorylation state of protein synthesis initiation faction eIF-2 during ischemia and recirculation, to evaluate the role of protein phosphorylation/dephosphorylation in the regulation of protein synthesis. Previous studies have demonstrated the direct role of hyperthermia in the reduction of brain protein synthesis activity in mice following amphetamine administration. We have now employed two-dimensional gel electrophoresis to demonstrate the synthesis of heat shock proteins during recovery from amphetamine-induced hyperthermia. We have determined that the unique sensitivity of the rabbit to the effects of electroconvulsive shock on protein synthesis in brain and other tissues arises from the hyperthermia produced by electroconvulsive shock in this species.